ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01850.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE The aim of this study was the endocrinological, enzymatic, and genetic evaluation of a family with a complex syndrome associating hypogonadotrophic hypogonadism with hyposmia, X‐linked Ichthyosis and renal malformation.DESIGN Hypothalamic‐pituritary‐testicular function, offaction, steroid sulphatase activity, and morphological renal studies were assessed. DNA molecular analyses were carried out In all the patients.PATIENTS Two brothers and their maternal uncle showed the clinical picture of congenital Ichthyosis, hypogonadism, hyposmia and unilateral renal maldevelopment. MEASUREMENTS LH and FSH were determined by RIA basally and after GnRH stimulation, and the test repeated after a period of GnRH priming. Testosterone response to hCG was measured. Arylsulphatase C assay was performed as a measure of steroid sulphatase activity. DNA amplification analysis and Southern blot analysis of four Xp22.3 loci were performed.RESULTS Low levels of gonadotophins, basally and after acute GnRH, Increased clearly after GnRH priming. Low testosterone levels Increased promptly after hCG. Subnormal levels of arylsulphatase C were detected. Hyposmia and renal hypoplasia or aplasia were demonstrated. A large Xp 22.3 deletion Including the genes responsible for X‐linked Ichthyosls (steroid sulphatase deficiency) and Kallmann syndrome was demonstrated.CONCLUSIONS The absence of the gene encoding steroid sulphatase accounts for the X‐linked Ichthyosis in these patients, whereas the absence of the Kallmann syndrome gene accounts for hypogonadism, anosmia and for the single kidney found In two of the three

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01851.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND AND OBJECTIVE Reduced serum levels of dehydroeplandrosterone sulphate (DHEAS) have been shown In patients with Cushing's syndrome resulting from adrenocortical adenoma, In contrast with normal DHEAS levels In patients with Cushing's disease. The elm of this study was to verify whether patients with incidentally discovered adrenocortical adenomas also have reduced levels of DHEAS.DESIGN Evaluation of serum DHEAS, serum and urinary cortisol, plasma ACTH and low dose dexamethasone suppression test In patients with adrenal Incidentaloma and Cushing's syndrome.PATIENTS Thirty‐two patients with adrenal Incidentaloma and, as controls, 17 patients with overt Cushing's syndrome, were studied.RESULTS Serum DHEAS levels lower than normal were found In 21/24 (81.5 %) patients with adrenocortical Incidentaloma, but In only 1/8 patients with a mass of non‐adrenocortical origin. This patient had massive bilateral metastatic infiltration of both adrenal glands and primary adrenal failure. The prevalence of low DHEAS levels in the two groups was significantly different (P= 00001). In patients with adrenocortical Incidentaloma, the prevalence of low DHEAS levels was significantly higher (P= 00001) than that found for some hormonal alterations Indicating pre‐clinical hypercortlsoilsm (high urinary cortisol, unsuppressed serum cortisol after low dose dexamethasone administration and low plasma ACTH). Low DHEAS levels were found in all patients with Cushing's syndrome due to adrenocortical adenoma but in none of those with Cushing's disease. CONCLUSIONS Our results Indicate that the finding of low DHEAS levels can be considered a marker of the adrenocortical origin of an adrenal Incidentaloma, provided adrenal failure has been exc

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01852.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND AND OBJECTIVE Ovarian Uh8SOnOgra‐phy may be helpful in distinguishing the various types of precocious puberty, and the ovarian appearances Increasingly influence choice of therapy In these girls. We examined retrospectively the ovarian volume and prevalence of polycystic ovarian appearance at ultrasound in girls with sexual precocity.DESIGN Ultrasound examinations were obtained from girls who presented with sexual precocity. If there were several scans from the same Individual, the latest was analysed.PATIENTS The girls were divided Into groups: untreated central precoclous puberty (n= 25), central precocious puberty treated with GnRH analogue (n= 18) or with GnRH analogue and recombinant human OH (n= 11), girls who had stopped treatment with GnRH analogue and GH (n= 12), premature thelarche and thelarche variant (n= 15) and premature adrenarche (n= 14).MEASUREMENTS Ovarian volume was calculated and the ovaries were assessed for polycystic appearance using standard criteria. Ovarian volume standard deviation (SD) scores were calculated using means and standard deviations derived from a control population and compared using analysis of variance. Differences from control data were assessed using Student's t‐test.RESULTS Ovarian volume SD scores for all the groups studied were greater than those for control subjects. Girls who had stopped treatment with GnRH analogue and GH had mean ovarian volume of 6.98 mi and ovarian volume SD score (+1·72) greater than that of girls having treatment with GnRH analogue alone (+1·24). Polycystic appearance ovaries were found in 83% of scans in girls who had stopped treatment with GnRH analogue and GH. The ovarian volume SD score of girls with premature adrenarche was less than that of girls with untreated central precoclous puberty.CONCLUSIONS Girls with central precocious puberty had large ovaries which did not return to a volume appropriate for age. Girls treated with GnRH analogue and GH developed very large ovaries when they stopped treatment, and had an Increased prevalence of ovaries with a polycystic appearance. Central precocious puberty, or some aspect of Its treatment, results In an Increased prevalence of polycystic ovarian appea

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01853.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Little Is known about the pattern of age‐related bone loss in men, and although androgens are required for optimum bone mass it Is not clear whether the fall in bone mass with age in men is related to failing androgens.DESIGN Cross‐sectional measurement of bone density, at five sites, and markers of bone resorption and formation in 147 normal volunteers aged 20‐83 years.SUBJECTS Healthy laboratory workers, hospital staff, their relatives, and husbands of women attending our osteoporosis clinic.MEASUREMENTS Forearm density (fat corrected), spine L2‐L4, femoral neck, Ward's triangle and trochanter density; serum procollagen I C‐terminal extension peptide, osteocalcin, bone alkaline phosphatase and collagen I C‐terminal telopeptlde; fasting urine hydroxy‐proline/creatinine, pyridinoline/creatinine and deoxy‐pyridinoline/creatinine; and free androgen Index (FAI), measured as serum testosterone/sex hormone binding globulin.RESULTS Bone loss accelerated at most sites after age 50. There was a significant fall In FAI from the third decade onwards. The levels of ail bone markers fell with age.CONCLUSIONS Bone loss In men appears to accelerate from age 50 and is associated with decreased bone formation which may be associated with falling levels o

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01854.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE We wished to study alterations In serum Insulin‐like growth factor‐I (IGF‐I) and its binding proteins in subjects with insulin dependent diabetes mellitus (IDDM) and possible relations with metabolic and GH secretory status, before and after cholinergic modulation. In addition, we have Investigated whether cholinergic modulation exerts any effects on IGF‐I secretion, Independently of any actions on GH secretory status.DESIGN All subjects received OH releasing hormone (GHRH) 1‐44; 80 μg i.v.) alone and 60 minutes following 120mg of pyridostigmine orally or 200 mg of plrenzepine orally. The three tests were carried out In random order at least one week apart. Blood was sampled at 15‐mInute Intervals over 120 minutes.PATIENTS Twelve male subjects with IDDM and no clinical evidence of complications were selected on the basis of HbA1levels to provide a wide range of metabolic control. SIX normal male subjects were also studied.MEASUREMENTS Serum IGF‐I, IGF‐binding protein 1 (IGFBP‐1) and IGFBP‐3 were measured at regular intervals throughout the study. Fasting plasma glucose and HbA1were measured before each study to provide measures of metabolic control.RESULTS Serum IGF‐I and IGFBP‐3 levels were significantly lower while serum IGFBP‐I levels were significantly higher In the diabetic subjects. Plrenzepine had no effect on serum IGF‐I, IGFBP‐1 or IGFBP‐3 In diabetic subjects but caused a significant Increase In serum IGF‐I and IGFBP‐3 levels in normal subjects.Pyridostigmine had no effect on IGF‐I, IGFBP‐1 or IGFBP‐3 In either diabetic or normal subjects. IGFBP‐1 levels were significantly correlated with fasting plasma glucose but no correlation was demonstrated between measures of diabetic control and serum IGF‐I or IGFBP‐3 levels In diabetic subjects, nor was there any correlation between OH responses to GHRH alone or after plrenzepine or pyridostigmine pretreatment and serum levels of IGF‐I, IGFBP‐1 or IGFBP‐3.CONCLUSION These data confirm that subjects with IDDM have reduced serum IGF‐I and IGFBP‐3 and Increased IGFBP‐1 levels, the latter being directly related to the fasting plasma glucose concentrations. The absence of any relation between changes In the IGF‐I system and altered GH neuroregulation after cholinergic modulation suggests that changes In IGF‐I are not the sole contributors to the altered GH neuroregulation which occurs In IDDM. We have also shown an acute stimulatory effect of pirenzepine on serum IGF‐I and IGFBP‐3 In normal subjects which

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01855.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Low dose cranial irradiation in children with acute lymphoblastic leukaemia (ALL) has been reported to reduce GH secretion in puberty. A recent study also reported a disturbed periodicity of GH secretion during puberty. We have focused on the different stages of puberty in studying these two parameters of GH secretion and have also compared the effects of 18vs24 Gy radiation dose.PATIENTS AND MEASUREMENTS Thirty‐four children previously treated for ALL were compared with a control group of 208 healthy normally growing children. GH secretion was measured as 24‐hour profiles. RESULTS In children treated for ALL, OH Secretion rate and OH peak amplitude were below the median values for controls, both before puberty and during all stages of puberty. The difference between patients and controls was most pronounced in late puberty. Radiation with 18 or 24 Gy gave similar results. However, time sequence analysis showed a similar periodicity of GH secretion in both patient and control groups before, as well as during, puberty. Thus, before puberty a broad range of cycles per 24 hours was seen. These synchronized during puberty to a predominant OH peak frequency of one every 3‐4 hours.CONCLUSIONS After low dose cranial irradiation with 18 or 24 Gy, the total amount of GH secreted is reduced both before and during puberty. We could not confirm previous findings of impaired periodicity of GH secretion in these Chi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01856.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE The increasing use In clinical practice of octreotide (a somatostatin analogue which inhibits the secretion of GH and other peptide hormones) led us to study the effects of this treatment on GH, Insulin‐like growth factors (IGF)‐I and II and IGF‐binding protein (IGFBP)‐3, as well as on circulating IGFBP complexes in acromegalic patients.DESIGN The circulating concentrations of GH, IGF‐I, IGF‐II and IGFBP‐3 were measured In acromegaiic patients before and after 3, 6, 9, and 12 months of treatment with octreotide (group I: n = 5), and compared with those found In a group of patients (group II) treated with bromocriptine (n= 3), cabergoline (n= 7) radiotherapy (n= 3) or surgical therapy (n= 2). In pools of serum obtained from patients treated with octreotide, dopaminergic drugs, surgery and radiation, before and after therapy, immunoreactive IGF‐I and IGFBP‐3 were also evaluated after Superdex 200 gel filtration in neutral conditions.RESULTS Before treatment, the concentration of IGF‐I and IGFBP‐3 were above the normal range in all patients, while IGF‐II levels were slightly reduced. After treatment with octreotide, IGF‐I (P= 0·004), IGF‐II (P= 0·02) and IGFBP‐3 (P<0·001) were significantly reduced as compared to basal levels. In subjects of group II, only IGF‐I concentration was significantly reduced by the treatment (P= 0.02), and a negative correlation between IGF‐I and IGF‐II concentrations was found (r=−0·58,P<0·0001). After gel filtration immunoreactive IGF‐I and IGFBP‐3 were found in the 150‐kDa mol.wt. region in serum obtained from untreated patients and from treated patients of group II, while in the serum of octreotide‐treated patients the IGF‐I and IGFBP‐3 peaks were shifted to the 60‐kDa mol.wt. region, thus suggesting that the acid‐lablle subunit of the 150‐kDa complex was drastically reduced. Since the GH concentrations in groups I and II were similar (M ± SEM; 13·8 ± 7·4 and 21·2±10·6mu/l respectively), the marked reduction in acid‐labile submit in the octreotide treated patients can be explained by a direct Inhibitory effect of somatostatin on the subunit.CONCLUSIONS Octreotide exerts an Inhibitory effect not only on IGF‐I but also on IGF‐II. The reduced formation of the 150‐kDa complex probably causes an increased metabolic clearance rate of IGF peptides which can account

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01857.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND AND OBJECTIVE Clinical acromegaly is Characterized by dysregulation of somatotroph GH secretion In the presence of high circulating serum IGF‐I levels. Physiologically, IGF‐I exerts a negative feedback on GH secretion at both the hypothalamic and the pituitary levels. We have previously shown that the 943 and 950 tyrosine residues In the IGF‐I receptor β‐subunit are required for ligand signalling to the GH gene, as substitution of these residues abrogates IGF‐I signal transduction. To determine whether a mutation within the IGF‐I receptor sub‐membrane domain may be Involved In the pathogenesis of GH secreting tumours, we studied this region In these tumours.DESIGN Exon 15 of the IGF‐I receptor containing both the 943 and 950 tyrosines was analysed In 19 GH‐secreting tumours by single‐strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products. Tumour DNA and patients’lymphocyte DNA, which served as normal controls, were analysed.RESULTS All samples exhibited normal migration patterns In the SSCP analysis which was further confirmed by direct DNA sequencing.CONCLUSIONS We conclude that mutations In the IGF‐I receptor sub‐membrane domain which disrupt the negative feedback loop are not Involved In the

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01858.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE In health, acute administration of dexamethasone (DEX) leads to growth hormone release. As sex steroids have a profound Influence on the somatotrophic axis, we decided to investigate the effects of DEX on OH release throughout the menstrual cycle.DESIGN A within subjects, randomized double‐blind counter‐balanced design was employed.METHODOLOGY Baseline levels Of GH, oestradiol and progesterone were taken at three the points In two consecutive menstrual cycles, after which 4mg of oral DEX or placebo was administered. Plasma samples for OH estimation were taken at 60,180,240 and 300 minutes. Each woman was tested 6 times, 3 times with placebo and 3 times with DEX.SUBJECTS Six women with regular menstrual cycles were studied.MEASUREMENTS Plasma OH, oestradiol and Progesterone were measured by radioimmunoassay. RESULTS When expressed as maximum change from base line (AGH) mean OH responses to DEX Increased Incrementally from early (12·2 ± 2·5 μ/I), through mid (25·6 ± 33 μ/I) to late (37·2 ± 3·5 μ/I) cycle. This represents a significant effect of cycle phase on GH responses to DEX (P<0.05). GH responses at both the mid‐cycle and the luteal the points are different from those during the follicular phase (P<0.05) and differences between mid‐cycle and luteal phases just fall to reach significance (P<015). Responses to placebo did not vary from baseline. Plasma oestradiol values were significantly correlated with GH responsivity to active drug throughout the cycle (P<0.05); the same was not true of progesterone. CONCLUSION Our study has demonstrated that dexa‐methasone‐mediated GH release shows a stepwise Increase througho

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01859.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY